Alzheimer's disease (AD) is the most common cause of dementia and there are no therapeutics effectively addressing the pathomechanism of this disease. The prevalence of AD is estimated to be 5.3 million cases in the USA (Alzheimer's Association 2009) and over 25 million cases worldwide. The prevalence of the disease is, moreover, expected to rise with the increasing average age of the global population. AD is caused by progressive accumulation of a toxic and hydrophobic β-amyloid (Aβ) peptide in the brain, which gradually effects loss of synapses, occurrence of neurofibrillary pathology, neuronal loss and eventually invokes symptoms of dementia. Accumulation of Aβ in the brain is driven by the inherent hydrophobicity of Aβ and its natural propensity to self-aggregate into toxic oligomers and fibers. Transgenic mice overexpressing human amyloid precursor protein mutant alone or together with a mutant of human presenilin 1 model early AD pathology and demonstrate profound memory impairment, which correlates with the presence of Aβ oligomers in the brain targeting NMDA receptors, but precedes timing of Aβ plaque formation. Despite the existing wealth of evidence pointing toward the deleterious effect of Aβ and Aβ oligomeric species in particular, there are no therapeutics available that effectively target the pathomechanism of AD.
Thus, there is an on-going need for development of effective therapeutic agents that target mechanisms of Aβ accumulation and toxicity in AD patients.